Definition
Lethal describes something that causes death. In microbiology and genetics, lethal factors are genes, mutations, organisms or doses of agents that result in death of cells or whole organisms.
Explanation
Lethality encompasses a range of contexts. In genetics, a lethal allele is an allele that prevents survival when present in a particular genotype; recessive lethal alleles such as the Agouti yellow mutation in mice cause embryonic death when homozygous, whereas dominant lethal mutations, like certain human huntingtin expansions, lead to late onset disease and death. Conditional lethal mutations are lethal only under specific conditions, such as temperature sensitive mutations used to study essential genes in microorganisms. In microbiology and toxicology, substances or microbes are described as lethal if they cause death at a given concentration or dose; botulinum neurotoxin is lethal to humans at nanogram levels, while many viruses have lethal strains that cause high mortality in susceptible hosts. Lethal effects depend on host species, age, route of exposure and immune status. In bacteriology, lethal factors may be components of toxin complexes, such as the lethal factor metalloprotease of Bacillus anthracis that inactivates MAP kinase kinases. The term lethal is also used in phage biology to denote infections that kill the host bacterium. Understanding lethal phenotypes and doses guides safety protocols, therapeutic design and population genetics models.
Illustrative cases and uses
• Recessive lethal alleles in mice, such as the Ay mutation, produce yellow coat colour in heterozygotes but are lethal in homozygous embryos.
• Dominant lethal alleles like the human HTT gene with long CAG repeats cause Huntington disease, leading to neurodegeneration and premature death.
• Conditional lethal mutants of viruses enable the study of essential genes by permitting replication at permissive temperatures but becoming lethal at restrictive temperatures.
• The lethal factor of anthrax toxin is a Zn2+ dependent protease that cleaves MAP kinase kinases, contributing to shock and death in systemic anthrax.
• Many bacteria and chemicals have lethal doses expressed as LD50 values, indicating the dose that kills 50 % of a test population.
The concept of lethality is central to genetics, toxicology and infectious disease, helping researchers classify mutations, design experiments and assess risks.
Related Terms: lethal dose, lethal allele, toxicity, virulence, mortality